Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state

Detalhes bibliográficos
Autor(a) principal: Rosset, Clévia
Data de Publicação: 2021
Outros Autores: Jaeger, Mariane da Cunha, Chiela, Eduardo Cremonese Filippi, Reis, Larissa Brussa, Sartor, Ivaine Tais Sauthier, Netto, Cristina Brinckmann Oliveira, Farias, Caroline Brunetto de, Roesler, Rafael, Prolla, Patrícia Ashton
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/233840
Resumo: Tuberous sclerosis complex (TSC) is an autosomal dominant cancer predisposition disorder caused by heterozygous mutations in TSC1 or TSC2 genes and characterized by mTORC1 hyperactivation. TSC-associated tumors develop after loss of heterozygosity mutations and their treatment involves the use of mTORC1 inhibitors. We aimed to evaluate cellular processes regulated by mTORC1 in TSC cells with different mutations before tumor development. Flow cytometry analyses were performed to evaluate cell viability, cell cycle and autophagy in non-tumor primary TSC cells with different heterozygous mutations and in control cells without TSC mutations, before and after treatment with rapamycin (mTORC1 inhibitor). We did not observe differences in cell viability and cell cycle between the cell groups. However, autophagy was reduced in mutated cells. After rapamycin treatment, mutated cells showed a significant increase in the autophagy process (p=0.039). We did not observe differences between cells with distinct TSC mutations. Our main finding is the alteration of autophagy in non-tumor TSC cells. Previous studies in literature found autophagy alterations in tumor TSC cells or knock-out animal models. We showed that autophagy could be an important mechanism that leads to TSC tumor formation in the haploinsufficiency state. This result could guide future studies in this field.
id UFRGS-2_99dac6a083aa3ce86f9db5b4044fecc4
oai_identifier_str oai:www.lume.ufrgs.br:10183/233840
network_acronym_str UFRGS-2
network_name_str Repositório Institucional da UFRGS
repository_id_str
spelling Rosset, CléviaJaeger, Mariane da CunhaChiela, Eduardo Cremonese FilippiReis, Larissa BrussaSartor, Ivaine Tais SauthierNetto, Cristina Brinckmann OliveiraFarias, Caroline Brunetto deRoesler, RafaelProlla, Patrícia Ashton2022-01-07T04:27:58Z20211415-4757http://hdl.handle.net/10183/233840001135318Tuberous sclerosis complex (TSC) is an autosomal dominant cancer predisposition disorder caused by heterozygous mutations in TSC1 or TSC2 genes and characterized by mTORC1 hyperactivation. TSC-associated tumors develop after loss of heterozygosity mutations and their treatment involves the use of mTORC1 inhibitors. We aimed to evaluate cellular processes regulated by mTORC1 in TSC cells with different mutations before tumor development. Flow cytometry analyses were performed to evaluate cell viability, cell cycle and autophagy in non-tumor primary TSC cells with different heterozygous mutations and in control cells without TSC mutations, before and after treatment with rapamycin (mTORC1 inhibitor). We did not observe differences in cell viability and cell cycle between the cell groups. However, autophagy was reduced in mutated cells. After rapamycin treatment, mutated cells showed a significant increase in the autophagy process (p=0.039). We did not observe differences between cells with distinct TSC mutations. Our main finding is the alteration of autophagy in non-tumor TSC cells. Previous studies in literature found autophagy alterations in tumor TSC cells or knock-out animal models. We showed that autophagy could be an important mechanism that leads to TSC tumor formation in the haploinsufficiency state. This result could guide future studies in this field.application/pdfengGenetics and molecular biology. Ribeirão Preto. Vol. 44, no. 4 (2021), e20200475, 8 p.Esclerose tuberosaAlvo mecanístico do complexo 1 de rapamicinaSobrevivência celularCiclo celularAutofagiaAutophagyMTOR inhibitorsNeurocutaneous disorderRapamycinTuberous Sclerosis ComplexPrimary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency stateinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/otherinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001135318.pdf.txt001135318.pdf.txtExtracted Texttext/plain37814http://www.lume.ufrgs.br/bitstream/10183/233840/2/001135318.pdf.txt0ae68991484acb0e72a2d95bc5c70380MD52ORIGINAL001135318.pdfTexto completo (inglês)application/pdf1667481http://www.lume.ufrgs.br/bitstream/10183/233840/1/001135318.pdfe3e19577392ca1ea3fb8cca6f3ad7ad5MD5110183/2338402023-11-15 04:24:52.907354oai:www.lume.ufrgs.br:10183/233840Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-11-15T06:24:52Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
title Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
spellingShingle Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
Rosset, Clévia
Esclerose tuberosa
Alvo mecanístico do complexo 1 de rapamicina
Sobrevivência celular
Ciclo celular
Autofagia
Autophagy
MTOR inhibitors
Neurocutaneous disorder
Rapamycin
Tuberous Sclerosis Complex
title_short Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
title_full Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
title_fullStr Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
title_full_unstemmed Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
title_sort Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
author Rosset, Clévia
author_facet Rosset, Clévia
Jaeger, Mariane da Cunha
Chiela, Eduardo Cremonese Filippi
Reis, Larissa Brussa
Sartor, Ivaine Tais Sauthier
Netto, Cristina Brinckmann Oliveira
Farias, Caroline Brunetto de
Roesler, Rafael
Prolla, Patrícia Ashton
author_role author
author2 Jaeger, Mariane da Cunha
Chiela, Eduardo Cremonese Filippi
Reis, Larissa Brussa
Sartor, Ivaine Tais Sauthier
Netto, Cristina Brinckmann Oliveira
Farias, Caroline Brunetto de
Roesler, Rafael
Prolla, Patrícia Ashton
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Rosset, Clévia
Jaeger, Mariane da Cunha
Chiela, Eduardo Cremonese Filippi
Reis, Larissa Brussa
Sartor, Ivaine Tais Sauthier
Netto, Cristina Brinckmann Oliveira
Farias, Caroline Brunetto de
Roesler, Rafael
Prolla, Patrícia Ashton
dc.subject.por.fl_str_mv Esclerose tuberosa
Alvo mecanístico do complexo 1 de rapamicina
Sobrevivência celular
Ciclo celular
Autofagia
topic Esclerose tuberosa
Alvo mecanístico do complexo 1 de rapamicina
Sobrevivência celular
Ciclo celular
Autofagia
Autophagy
MTOR inhibitors
Neurocutaneous disorder
Rapamycin
Tuberous Sclerosis Complex
dc.subject.eng.fl_str_mv Autophagy
MTOR inhibitors
Neurocutaneous disorder
Rapamycin
Tuberous Sclerosis Complex
description Tuberous sclerosis complex (TSC) is an autosomal dominant cancer predisposition disorder caused by heterozygous mutations in TSC1 or TSC2 genes and characterized by mTORC1 hyperactivation. TSC-associated tumors develop after loss of heterozygosity mutations and their treatment involves the use of mTORC1 inhibitors. We aimed to evaluate cellular processes regulated by mTORC1 in TSC cells with different mutations before tumor development. Flow cytometry analyses were performed to evaluate cell viability, cell cycle and autophagy in non-tumor primary TSC cells with different heterozygous mutations and in control cells without TSC mutations, before and after treatment with rapamycin (mTORC1 inhibitor). We did not observe differences in cell viability and cell cycle between the cell groups. However, autophagy was reduced in mutated cells. After rapamycin treatment, mutated cells showed a significant increase in the autophagy process (p=0.039). We did not observe differences between cells with distinct TSC mutations. Our main finding is the alteration of autophagy in non-tumor TSC cells. Previous studies in literature found autophagy alterations in tumor TSC cells or knock-out animal models. We showed that autophagy could be an important mechanism that leads to TSC tumor formation in the haploinsufficiency state. This result could guide future studies in this field.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2022-01-07T04:27:58Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/other
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10183/233840
dc.identifier.issn.pt_BR.fl_str_mv 1415-4757
dc.identifier.nrb.pt_BR.fl_str_mv 001135318
identifier_str_mv 1415-4757
001135318
url http://hdl.handle.net/10183/233840
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.pt_BR.fl_str_mv Genetics and molecular biology. Ribeirão Preto. Vol. 44, no. 4 (2021), e20200475, 8 p.
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFRGS
instname:Universidade Federal do Rio Grande do Sul (UFRGS)
instacron:UFRGS
instname_str Universidade Federal do Rio Grande do Sul (UFRGS)
instacron_str UFRGS
institution UFRGS
reponame_str Repositório Institucional da UFRGS
collection Repositório Institucional da UFRGS
bitstream.url.fl_str_mv http://www.lume.ufrgs.br/bitstream/10183/233840/2/001135318.pdf.txt
http://www.lume.ufrgs.br/bitstream/10183/233840/1/001135318.pdf
bitstream.checksum.fl_str_mv 0ae68991484acb0e72a2d95bc5c70380
e3e19577392ca1ea3fb8cca6f3ad7ad5
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)
repository.mail.fl_str_mv
_version_ 1801225048095195136